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Synthesis And Characterization of Phenytoin Drug And Alpha

Benzilmonoxime From BEA711

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 International Journal of Medical Works
Kambohwell Publisher Enterprises
www.kwpublisher.com
Synthesis And Characterization of Phenytoin Drug And Alpha
Benzilmonoxime From BEA711
Jamila khan, Arifullah khan, Tahirabashir
Abstract—Phenytoin was prepared by the reaction of benzil
with urea in the presence of sodiumhydroxide. Alpha
benzilmonoxime was prepared by the reaction of benzil with
hydroxylamine hydrochloride in the presence of
sodiumhydroxide and ethanol. U.V techniques had been
utilized to observe the maximum absorption wavelength to
identify the chromophoric groups present in the molecule of
phenytoin and alpha benzilmonoxime. Melting point was taken
to determine the purity of these compounds. FT-IR had been
used for the determination of functional groups present in the
molecule of synthesized derivatives. Percentage yield was also
determined.
Keywords— Benzil. Phenytoin, Alpha-Benzilmonoxime,
Hydroxylamine hydrochloride, Urea, Sodiumhydroxide
I. INTRODUCTION
Benzil is a a-diketone and an organic compound. Diketone
have the two ketonic groups and have two alkyl groups which
may be same or different such as benzil which have the same
phenyl groups. Benzil is a yellow crystalline solid. Its m.p is
95°C. It has the long C-C bond which is 1.5A°. The PhCO
centers are planar. The benzoyl group pairs are twisted with
respect to each other and having the 11 rdihederal angle. The
molecular formula of benzil is (C6H5C0)2 [ I ].
Benzil is used to form the phenytoin which is medicme in
the treatment of epilepsy It is used as a photosensitive agent in
photo curable coatings, as a precursors for some
pharmaceutically important compound such as the antiepileptic
phenytoin and anticonvulsant dilantin, as a aluminum
electrolytic capacitors [2.3]. asa potent activator of microsomal
epoxide hydrolase in vitro, as a photosensitive agent. It is
unique because it produces a large number of reduction
products [4,5]. Benzilsare used as inhibitors of carboxyl
esterase enzymes, proteins involved in the metabolism of
esterified drugs and xenobiotics.
Phenytoin is the oldestnonsedativeantiseizure drug. It is
also known as muscle relaxant and anti-arrythmic. It is an
antiepileptic drug which is also called anticonvulsant. The
concentration of phenytoin must be maintained in the plasma
[6]. Phenytoin is composed of five membered hydantoin with
two phenyl groups at the five positions. Phenytoin has three
member molecule associated with urea and although has
Jamila wazir: Gomal university ,Dera Ismail Khan.
Email:jamilawazir.18@gmail.com.
Arif ullah khan: Shifa College of Nursing ,Islamabad. Pakistan.
Tahira bashir: government college university Faisalabad. Pakistan
Copyright © 2015 KWP Journals. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Vol. 1, Issue 2, PP. 5-8, Nov. 2015
pharmacological tool. It is an anticonvulsant and used to treat
various types of disorders such as epilepsy. Phenytoin is an
antiepileptic drug which decreases the action of epilepsy. It
plays the important role in controlling the action of brain and
nervous system during the treatment of epilepsy. It reduces the
flow of calcium and sodium ions and at high frequency the
flow of neurons is low which causes to prevent from the
electrical activity of seizure. Phenytoin reduces the release of
neurotransmitter and glutamate through them the body's central
nervous system is stimulated and increases the release of
GABA through it the body's central nervous system is
suppressant. The first action of Phenytoin is decrease the effect
of seizure on motor cortex. Epilepsy caused by the rapid flow
of sodium ions from neurons. It decreases the flow of sodium
ions by the release of GABA .Threshold is stabilized by
phenytoin against the extraordinary energetic excitability
occurred due to the environmental changes thus it reduces the
membrane potential gradient which causes the loss of post-
tetanic potentiation. Due to this losing cortex area has been
prevented from cortical seizure foci. Due to the effect of
chlonic seizure it reduces the action of brain stem centers. It
blocks the voltage sodium channel in neurons. By this action
neurological electrical recovery is delay from inactivation. The
inhibitory effect of phenytoin is depend on folic acid. The data
was published by Putnam Merrit in 1938 in which they use
phenytoin for the treatment of seizures. Thus phenytoin
appeared as an anticonvulsant agent at that time. More than
hundred diseases cured by phenytoin. They also found that it
has been used for the treatment of ulcers and many other
diseases due to its inhibitory effect on collagenase, facilitating
collagen deposition and also have a major effect on immune
system. It is distributed to muscles, into central nervous
system, fat and brain tissue where in endoplasmic reticulum it
cumulate [4]. a-Benzilmonoxime is a derivative of benzil. It is
known as chelating agent and having the special interest due to
their biological activities and semi-conducting properties. a-
Benzilmonoxime have the importance due to their
physiochemical properties and their reactivity patterns [12].
II. RESEARCH ELABORATIONS
The Benzil(97%),urea(95%) and ethanol(99.8%),
concentrated hydrochloric acid(98%) were obtained from
MERCK and used as received. Sodium-hydroxide (99%) was
obtained from Riedel-Dehaen, Glacial acetic acid(100%) from
Sigma-Alorich, Phenyl hydrazine(99%) was obtained from
china. Hydroxylamine hydrochloride(99%) British Drug
House(BDH).
 Spvthesisof phenytoin test were performed for the identification of phenytoin which
was given in table 1.
EOUATION
TABLE NO:1
THE CHEMICAL TEST FOR PHENITOIN

Experiment Observation inference

Dissolve 20mg in A white Phenytoin

2m1 of ammonia and precipitate is is
Benzilphenytom add 5m1 of produced Confirmed
silver nitrate
PROCEDURE
5.25g (0.025M) of benzil, Ig(0.025M) of Na0H in 100m1 Dissolve 5mg in Iml Phenytoin
A blue violet
of water,I.5g(0.025M) urea in 50m1 ethanol were taken in of boiling ethanol+2 is
colour is
250m1 of round bottom flask. The round bole flask was droops confirmed
produced
equipped with a reflux condenser Mixture was heated under or copper (II)
reflux on a steam bath for 3-hours. This mixture was allowed to sulphate and allow to
cool at room temperature and poured the reaction mixture in a-Benzilmonoxime
cool. was synthesized by the reaction of benztl
100m1 of cold water. The solution was filtered and acidified with phenyl-hydrazinehyrochloride in the presence of ethanol
the filtrate with concentrated hydrochloric acid. White and sodium-hydroxide. Pure a-Benzilmonoxime was obtained
precipitates, m.p. 293 oC, formed filtered and washed with by the recrystallization of crude a-Benzilmonoxime with
water, recrystalized with ethanol. ethanol. They were characterized by the FTIR. UV-VIS
spectroscopy and melting point. The melting point of this
SENTHESIS OF a- BENZILMONOXIME comp0d was determined by the use of Gallenhamp melting
EOUATION point apparatus. The physical properties of these were given in
table 2.
TABLE NO:2
PHYSICAL PROPERTIES OF PHENYTOIN AND ALPHA
BENZILMONOXIME
Mol.for Percentag
Color Melti
mula e
Name and ng
and yield
Phase points
weight
PROCEDURE C15H12N 71%
White
21g (0.1M) of benzil was taken in beaker and little ethanol phenyton 2 O2 2930
solid
was added to make a little thin paste. Concentrated aqueous 252.3
solution of 6.9g (0.1M) of hydroxylamine hydrochloride was C14H11N Light 82%
also added in this mixture and cooled the mixture in ice salt AplhaBenzilmonoxi 1370
O2 pinkS
bath at -5 °C. Then 20% of 15g sodium hydroxide was added me
225.24 olid
drop-wise with rapid mechanical stirring. This procedure was
continued for 90 minutes. The temperature must be maintained
and was not risen above 0°C. After 90 minutes it was diluted The structure of all synthesized compounds was determined
with water. Filteration was done by sintered glass funnel to by the FTIR. FTIR-Spectra of phenytoin showed that the broad
remove the small quantity of unchanged benzil. Filtrate was peak for C-N observed at 1342.95. This was the major group in
acidified with glacial acetic acid. It was allowed to stand for 30 phenytoin. Peak came at 744,22 which indicated that CH bond
minutes Filtered the a-benzilmonoxime and recrystalized from was present. The peak came at 1513 which indicated that C-C
ethanol. Yield was 82% and M P. 137°C.Equations bond was present. The peak which came at 1572.18 which
indicated that bond was present. These peaks showed that
III. RESULTS aromatic ring was present which was phenyl group.The peaks
Phenytoin was synthesized by the reaction of benzil with which came atl 342.95 indicated that C-N bond was present.
urea in the presence of sodium hydroxide. There were These peaks showed that amide group is present. Thus the
impurities in phenytoin. Impurities were removed by washing structure of phenytoin was confirmed by all these peaks which
with water and then recrystallized the phenytoin with ethanol. came in FTIR-Spectra. The FTIR absorption of different
Then pure form of phenytoin was obtained. It was formed by chemical bonds/functional groups of phenytoin were shown in
addition and condensation mechanism. After recrystalization table no: 3.
white crystals of phenytoin was obtained. Different chemical TABLE NO :3

International Journal of Medical Works Vol. 1, Issue 2, PP. 4-8, Nov. 2015
 FTIR ABSORPTION BANDS OF DIFFERENT
CHEMICAL BONDS/FUNCTIONAL GROUPS OF
PHENYTION
Range of
Observed
Functional Chemical Type of peaks
peaks
group bond vibration (cm⁻ ¹)
(cm⁻ ¹)
Amide C=O Stretching 1692.06 1680˗1700
Phenyl C-H Stretching 744.22 730˗770
Amide N-H Bending 1598.07 1500˗1650
Amide C-N Stretching 1331.79 1280˗1350
Phenyl C-C Stretching 1513.03 1506
Phenyl C=C Stretching 1527.18 1580

MR-SPECTRA OF ALPILI-BENZIL MONOXIME

The UV-VIS spectroscopy is also used for the identification
of compound which was given in table.
TABLE.5:

The λmax And Absorbance of Alpha-Benzilmonoxime

ƛ max
Name of Derivatives Absorbance
(nm)
Alpha-
305 2.374
Benzilmonoxime
FTIR SPECTRA OF PHENYTOIN The 2max And Absorbance OfAlaph-Ben„ilrn,nv,xune.
FTIR spectra of a-benzilmonoxime showed that the broad
peak for C=N observed at 1620.04, for OH at 3200.07 which
indicated that oxime group was present. Different peaks of this IV. CONCLUSION
compound were observed such as CH peak at 730.07, C=C
peak at 1570.08 and C-C peak at 1511.07.A11 these Phenytoin and Alpha-benzilmonxime have been prepared in
bands/peaks showed that phenyl group was present. The CO the laboratory. They are playing important role in industry,
peak came at 1685 which showed that ketonic group was biomedical fields, extraction and analytical chemistry.
present.The FTIR absorption of different chemical Phenytoin is the famous derivative of benzil which is widely
bonds/functional groups of phenytoin were shown in table no used for the treatment of different diseases_ Structure
4. determination of benzil derivatives were obtained by the use
of FTIR and UV-VIS spectroscopy. FTIR spectra of
TABLE NO 4: Phenytoin showed the peak for C-N at 1342.95 cm's and for
F77R absorption bands of different chemical bonds/ CO at 1692.06 cm'', FTIR spectra of a-Benzilmonoxime
functional groups of alpha-benzilmonoxime showed the peak for OH at 3200.07 cnil and for CO at 1685
em's. UV technique was also applied on determining the
Observed Range of maximum absorbance Alpha-benzilmonoxime which was
Chemical Type of peaks
Functional peaks 2.374. Thus the structures of benzil derivatives were
bond vibration (cm⁻ ¹)
group (cm⁻ ¹) determined.
3150-
Oxime O-H Stretching 3200.07
3300
1675- REFERENCES
Ketone CO Stretching 1685.00
1690
1620- [1] Finar, i.l. "organic chemistry (the fiindamental principle)", 6th ed.,
Oxime C=N Stretching 1620.04 pearson education, ltd, pp.792 (1973).
1690
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1506 chemistry, 41:1659-1663(2011).
Phenyl C-C Stretching 1511.07
[3] Berberich, l.j. And friedman, r. Dielectric, us2525473 a, (1950).
Phenyl C=C Stretching 1570.08 1580

International Journal of Medical Works Vol. 1, Issue 2, PP. 4-8, Nov. 2015
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International Journal of Medical Works Vol. 1, Issue 2, PP. 4-8, Nov. 2015

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